Jakab Balázs, Helyes Zsuzsanna, Varga Angelika, Bölcskei Kata, Szabó Arpád, Sándor Katalin, Elekes Krisztián, Börzsei Rita, Keszthelyi Dániel, Pintér Erika, Petho Gábor, Németh József, Szolcsányi János
Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, H-7643, Pécs, Szigeti u. 12, Hungary.
Eur J Pharmacol. 2005 Jul 4;517(1-2):35-44. doi: 10.1016/j.ejphar.2005.05.002.
The TRPV1 capsaicin receptor is an integrator molecule on primary afferent neurones participating in inflammatory and nociceptive processes. The present paper characterizes the effects of JYL1421 (SC0030), a TRPV1 receptor antagonist, on capsaicin-evoked responses both in vitro and in vivo in the rat. JYL1421 concentration-dependently (0.1-2 microM) inhibited capsaicin-evoked substance P, calcitonin gene-related peptide and somatostatin release from isolated tracheae, while only 2 microM resulted in a significant inhibition of electrically induced neuropeptide release. Capsazepine (0.1-2 microM), as a reference compound, similarly diminished both capsaicin-evoked and electrically evoked peptide release. JYL1421 concentration-dependently decreased capsaicin-induced Ca(2+) accumulation in cultured trigeminal ganglion cells, while capsazepine was much less effective. In vivo 2 mg/kg i.p. JYL1421, but not capsazepine, inhibited capsaicin-induced hypothermia, eye wiping movements and reflex hypotension (a component of the pulmonary chemoreflex or Bezold-Jarisch reflex). Based on these data JYL1421 is a more selective and in most models also a more potent TRPV1 receptor antagonist than capsazepine, therefore it may promote the assessment of the (patho)physiological roles of the TRPV1 receptor.
TRPV1辣椒素受体是初级传入神经元上参与炎症和伤害感受过程的整合分子。本文描述了TRPV1受体拮抗剂JYL1421（SC0030）对大鼠体内外辣椒素诱发反应的影响。JYL1421浓度依赖性地（0.1 - 2微摩尔）抑制辣椒素诱发的P物质、降钙素基因相关肽和生长抑素从离体气管的释放，而只有2微摩尔能显著抑制电诱导的神经肽释放。作为参考化合物的辣椒平（0.1 - 2微摩尔）同样减少了辣椒素诱发和电诱发的肽释放。JYL1421浓度依赖性地降低培养的三叉神经节细胞中辣椒素诱导的Ca(2+)积累，而辣椒平的效果则差得多。在体内，腹腔注射2毫克/千克的JYL1421而非辣椒平，可抑制辣椒素诱导的体温过低、擦眼动作和反射性低血压（肺化学反射或贝佐尔德 - 雅里什反射的一个组成部分）。基于这些数据，JYL1421是一种比辣椒平更具选择性且在大多数模型中也更有效的TRPV1受体拮抗剂，因此它可能有助于评估TRPV1受体的（病理）生理作用。
